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Administrative data

Description of key information

Acute oral LD50 in rats: 4523 mg/kg bw. 
Acute inhalation LC50 in rats >20.8 mg/l.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
4 523 mg/kg bw

Additional information

oral

In a reliable acute oral study in rats the LD50 was determined to be 4523 mg/kg bw (BASF AG, 1968). The reliability of this study is marginally limited by the short post-application observation period (7 days), which in this case does not affect the basis for classification. No classification is indicated according to current EU regulations (GHD/DSD). Severe but reversible signs of toxicity (staggering gait, apathy, side and prone position, dyspnea) were reported between 2000 mg/kg bw and the LC50.

inhalation

In a recent OECD 403 acute inhalation guideline study neither mortality nor significant signs of systemic toxicity were observed in rats head/nose exposed for 4h to vapors at the limit dose of 20.8 mg/l (BASF AG, 2010). In the same study potential morphological changes in the respiratory tract were evaluated in a satellite group (3 male rats). This satellite group was exposed to the test substance simultaneously with the main group animals and the animals were sacrificed on post exposure study day 2. No indications for a respiratory irritation were identified. Therefore no classification is indicated according to current EU regulations (GHS/DSD).

 

In an old inhalation risk test rats were whole body exposed to a test atmosphere saturated with vapors of dioxpane at 20°C (BASF AG, 1968). The value of this assay for classification is limited, since exposure was for 30 min and 1 h only and the test atmosphere was not analytically determined. From substance loss the nominal concentration described in the report was calculated as 103.1 mg/l. With the vapor pressure of 22.6 hPa a saturated vapor concentration of 95.1 mg/l can be calculated. At this concentration 5/6 animals died after 60min exposure time, but no conclusion can be derived for the toxicity of dioxepane at the limit dose (20mg/l).

dermal

No relevant experimental study investigating the acute dermal toxicity of dioxepane is available.

However, a reliable prediction of the potential acute dermal toxicity and the respective classification and labeling of the substance is possible based on the physico-chemical properties of the test substance and data generated in other toxicological studies. Performing a dermal toxicity study would not create new toxicological information and is therefore not in accordance with animal welfare ideals.

The chosen approach described below is also in line with a recent publication (Creton, St. et al, Critical reviews in Toxicology, 2010, Vol. 40 No.1, pages 50-83), in which the general benefit of performing acute dermal toxicity studies is questioned, if there are no indications for a substance to be more toxic via dermal than via oral route.

For dioxepane the acute toxicity was assayed by reliable studies on two exposure routes and no indications of severe systemic toxicity were identified.

 

Justification for classification or non-classification

Based on an acute oral LD50 in rats of 4523 mg/kg bw and an acute inhalation LC50 in rats >20.8 mg/l no classification is required for acute toxicity according to EU regulations (GHS/DSD).